title: Immunostimulatory activity of dendritic cells pulsed with carbonic anhydrase IX and Acinetobacter baumannii outer membrane protein A for renal cell carcinoma.
abstract: Dendritic cell (DC)-based immunotherapy is a potent therapeutic modality for treating renal cell carcinoma (RCC), but development of antigens specific for tumor-targeting and anti-tumor immunity is of great interest for clinical trials. The present study investigated the ability of DCs pulsed with a combination of carbonic anhydrase IX (CA9) as an RCC-specific biomarker and Acinetobacter baumannii outer membrane protein A (AbOmpA) as an immunoadjuvant to induce anti-tumor immunity against murine renal cell carcinoma (RENCA) in a murine model. Murine bone-marrow-derived DCs pulsed with a combination of RENCA lysates and AbOmpA were tested for their capacity to induce DC maturation and T cell responses in vitro. A combination of RENCA lysates and AbOmpA up-regulated the surface expression of co-stimulatory molecules, CD80 and CD86, and the antigen presenting molecules, major histocompatibility (MHC) class I and class II, in DCs. A combination of RENCA lysates and AbOmpA also induced interleukin-12 (IL-12) production in DCs. Next, the immunostimulatory activity of DCs pulsed with a combination of CA9 and AbOmpA was determined. A combination of CA9 and AbOmpA up-regulated the surface expression of co-stimulatory molecules and antigen presenting molecules in DCs. DCs pulsed with a combination of CA9 and AbOmpA effectively secreted IL-12 but not IL-10. These cells interacted with T cells and formed clusters. DCs pulsed with CA9 and AbOmpA elicited the secretion of interferon-γ and IL-2 in T cells. In conclusion, a combination of CA9 and AbOmpA enhanced the immunostimulatory activity of DCs, which may effectively induce anti-tumor immunity against human RCC.
authors.affiliation: Department of Physiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Kim
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Yang
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Dong Chan
authors.initials: DC
authors.lastname: Moon
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Je Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Duk Yoon
authors.initials: DY
authors.lastname: Kim
mesh_terms: D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000628:therapy; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10; C078167:OMPA outer membrane proteins; D018664:Interleukin-12; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases